CN1846703A - Vagina administration mifepristone prepn and its composition and prepn process - Google Patents
Vagina administration mifepristone prepn and its composition and prepn process Download PDFInfo
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- CN1846703A CN1846703A CN 200610042252 CN200610042252A CN1846703A CN 1846703 A CN1846703 A CN 1846703A CN 200610042252 CN200610042252 CN 200610042252 CN 200610042252 A CN200610042252 A CN 200610042252A CN 1846703 A CN1846703 A CN 1846703A
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- Prior art keywords
- mifepristone
- preparation
- vagina administration
- host
- vagina
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Links
- 229960003248 mifepristone Drugs 0.000 title claims abstract description 58
- VKHAHZOOUSRJNA-GCNJZUOMSA-N mifepristone Chemical compound C1([C@@H]2C3=C4CCC(=O)C=C4CC[C@H]3[C@@H]3CC[C@@]([C@]3(C2)C)(O)C#CC)=CC=C(N(C)C)C=C1 VKHAHZOOUSRJNA-GCNJZUOMSA-N 0.000 title claims abstract description 58
- 210000001215 vagina Anatomy 0.000 title claims abstract description 32
- 239000000203 mixture Substances 0.000 title claims description 18
- 238000002360 preparation method Methods 0.000 claims abstract description 42
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 12
- 239000000546 pharmaceutical excipient Substances 0.000 claims abstract description 10
- 239000002904 solvent Substances 0.000 claims abstract description 10
- 239000004094 surface-active agent Substances 0.000 claims abstract description 8
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 24
- -1 hydroxypropyl Chemical group 0.000 claims description 23
- 238000003756 stirring Methods 0.000 claims description 22
- 239000003814 drug Substances 0.000 claims description 19
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 claims description 15
- 229920002125 Sokalan® Polymers 0.000 claims description 14
- AXTGDCSMTYGJND-UHFFFAOYSA-N 1-dodecylazepan-2-one Chemical class CCCCCCCCCCCCN1CCCCCC1=O AXTGDCSMTYGJND-UHFFFAOYSA-N 0.000 claims description 10
- 230000008961 swelling Effects 0.000 claims description 10
- 230000002421 anti-septic effect Effects 0.000 claims description 9
- 229940079593 drug Drugs 0.000 claims description 9
- 239000003961 penetration enhancing agent Substances 0.000 claims description 9
- 229960003639 laurocapram Drugs 0.000 claims description 8
- NIXOWILDQLNWCW-UHFFFAOYSA-N Acrylic acid Chemical compound OC(=O)C=C NIXOWILDQLNWCW-UHFFFAOYSA-N 0.000 claims description 7
- 229960001631 carbomer Drugs 0.000 claims description 7
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 6
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 6
- 229920002153 Hydroxypropyl cellulose Polymers 0.000 claims description 6
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 6
- 229920003171 Poly (ethylene oxide) Polymers 0.000 claims description 6
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 claims description 6
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 claims description 6
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 6
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 claims description 6
- 239000002552 dosage form Substances 0.000 claims description 6
- 150000002148 esters Chemical class 0.000 claims description 6
- 239000002047 solid lipid nanoparticle Substances 0.000 claims description 6
- GSEJCLTVZPLZKY-UHFFFAOYSA-N Triethanolamine Chemical compound OCCN(CCO)CCO GSEJCLTVZPLZKY-UHFFFAOYSA-N 0.000 claims description 5
- 239000003795 chemical substances by application Substances 0.000 claims description 5
- 238000001035 drying Methods 0.000 claims description 5
- LXCFILQKKLGQFO-UHFFFAOYSA-N methylparaben Chemical compound COC(=O)C1=CC=C(O)C=C1 LXCFILQKKLGQFO-UHFFFAOYSA-N 0.000 claims description 5
- 238000002156 mixing Methods 0.000 claims description 5
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 4
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 4
- 239000004372 Polyvinyl alcohol Substances 0.000 claims description 4
- 235000011572 Pyrus ussuriensis Nutrition 0.000 claims description 4
- 244000173166 Pyrus ussuriensis Species 0.000 claims description 4
- 229920002472 Starch Polymers 0.000 claims description 4
- 239000002671 adjuvant Substances 0.000 claims description 4
- 239000000783 alginic acid Substances 0.000 claims description 4
- 235000010443 alginic acid Nutrition 0.000 claims description 4
- 229920000615 alginic acid Polymers 0.000 claims description 4
- 229960001126 alginic acid Drugs 0.000 claims description 4
- 150000004781 alginic acids Chemical class 0.000 claims description 4
- 239000004359 castor oil Substances 0.000 claims description 4
- 235000019438 castor oil Nutrition 0.000 claims description 4
- OSASVXMJTNOKOY-UHFFFAOYSA-N chlorobutanol Chemical compound CC(C)(O)C(Cl)(Cl)Cl OSASVXMJTNOKOY-UHFFFAOYSA-N 0.000 claims description 4
- ZEMPKEQAKRGZGQ-XOQCFJPHSA-N glycerol triricinoleate Natural products CCCCCC[C@@H](O)CC=CCCCCCCCC(=O)OC[C@@H](COC(=O)CCCCCCCC=CC[C@@H](O)CCCCCC)OC(=O)CCCCCCCC=CC[C@H](O)CCCCCC ZEMPKEQAKRGZGQ-XOQCFJPHSA-N 0.000 claims description 4
- 229940074046 glyceryl laurate Drugs 0.000 claims description 4
- 239000001863 hydroxypropyl cellulose Substances 0.000 claims description 4
- 235000010977 hydroxypropyl cellulose Nutrition 0.000 claims description 4
- 239000012528 membrane Substances 0.000 claims description 4
- 229920002451 polyvinyl alcohol Polymers 0.000 claims description 4
- 239000008107 starch Substances 0.000 claims description 4
- 235000019698 starch Nutrition 0.000 claims description 4
- LWZFANDGMFTDAV-BURFUSLBSA-N [(2r)-2-[(2r,3r,4s)-3,4-dihydroxyoxolan-2-yl]-2-hydroxyethyl] dodecanoate Chemical compound CCCCCCCCCCCC(=O)OC[C@@H](O)[C@H]1OC[C@H](O)[C@H]1O LWZFANDGMFTDAV-BURFUSLBSA-N 0.000 claims description 3
- NOOLISFMXDJSKH-UTLUCORTSA-N (+)-Neomenthol Chemical compound CC(C)[C@@H]1CC[C@@H](C)C[C@@H]1O NOOLISFMXDJSKH-UTLUCORTSA-N 0.000 claims description 2
- DTGKSKDOIYIVQL-WEDXCCLWSA-N (+)-borneol Chemical compound C1C[C@@]2(C)[C@@H](O)C[C@@H]1C2(C)C DTGKSKDOIYIVQL-WEDXCCLWSA-N 0.000 claims description 2
- WRIDQFICGBMAFQ-UHFFFAOYSA-N (E)-8-Octadecenoic acid Natural products CCCCCCCCCC=CCCCCCCC(O)=O WRIDQFICGBMAFQ-UHFFFAOYSA-N 0.000 claims description 2
- IEQAICDLOKRSRL-UHFFFAOYSA-N 2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-(2-dodecoxyethoxy)ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethanol Chemical compound CCCCCCCCCCCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCO IEQAICDLOKRSRL-UHFFFAOYSA-N 0.000 claims description 2
- LQJBNNIYVWPHFW-UHFFFAOYSA-N 20:1omega9c fatty acid Natural products CCCCCCCCCCC=CCCCCCCCC(O)=O LQJBNNIYVWPHFW-UHFFFAOYSA-N 0.000 claims description 2
- QSBYPNXLFMSGKH-UHFFFAOYSA-N 9-Heptadecensaeure Natural products CCCCCCCC=CCCCCCCCC(O)=O QSBYPNXLFMSGKH-UHFFFAOYSA-N 0.000 claims description 2
- 229920002134 Carboxymethyl cellulose Polymers 0.000 claims description 2
- GHXZTYHSJHQHIJ-UHFFFAOYSA-N Chlorhexidine Chemical compound C=1C=C(Cl)C=CC=1NC(N)=NC(N)=NCCCCCCN=C(N)N=C(N)NC1=CC=C(Cl)C=C1 GHXZTYHSJHQHIJ-UHFFFAOYSA-N 0.000 claims description 2
- NOOLISFMXDJSKH-UHFFFAOYSA-N DL-menthol Natural products CC(C)C1CCC(C)CC1O NOOLISFMXDJSKH-UHFFFAOYSA-N 0.000 claims description 2
- 241000196324 Embryophyta Species 0.000 claims description 2
- 239000004354 Hydroxyethyl cellulose Substances 0.000 claims description 2
- 229920000663 Hydroxyethyl cellulose Polymers 0.000 claims description 2
- 229920001612 Hydroxyethyl starch Polymers 0.000 claims description 2
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 claims description 2
- 229920000881 Modified starch Polymers 0.000 claims description 2
- 241001597008 Nomeidae Species 0.000 claims description 2
- 239000005642 Oleic acid Substances 0.000 claims description 2
- ZQPPMHVWECSIRJ-UHFFFAOYSA-N Oleic acid Natural products CCCCCCCCC=CCCCCCCCC(O)=O ZQPPMHVWECSIRJ-UHFFFAOYSA-N 0.000 claims description 2
- 229960000583 acetic acid Drugs 0.000 claims description 2
- 239000002253 acid Substances 0.000 claims description 2
- WNROFYMDJYEPJX-UHFFFAOYSA-K aluminium hydroxide Chemical compound [OH-].[OH-].[OH-].[Al+3] WNROFYMDJYEPJX-UHFFFAOYSA-K 0.000 claims description 2
- 229910021502 aluminium hydroxide Inorganic materials 0.000 claims description 2
- 239000001768 carboxy methyl cellulose Substances 0.000 claims description 2
- 235000010948 carboxy methyl cellulose Nutrition 0.000 claims description 2
- 125000002057 carboxymethyl group Chemical group [H]OC(=O)C([H])([H])[*] 0.000 claims description 2
- 239000008112 carboxymethyl-cellulose Substances 0.000 claims description 2
- 239000001913 cellulose Substances 0.000 claims description 2
- 229920002678 cellulose Polymers 0.000 claims description 2
- 229960004926 chlorobutanol Drugs 0.000 claims description 2
- DTPCFIHYWYONMD-UHFFFAOYSA-N decaethylene glycol Polymers OCCOCCOCCOCCOCCOCCOCCOCCOCCOCCO DTPCFIHYWYONMD-UHFFFAOYSA-N 0.000 claims description 2
- 239000012362 glacial acetic acid Substances 0.000 claims description 2
- 125000005456 glyceride group Chemical group 0.000 claims description 2
- 229940027278 hetastarch Drugs 0.000 claims description 2
- 235000019447 hydroxyethyl cellulose Nutrition 0.000 claims description 2
- 229940071826 hydroxyethyl cellulose Drugs 0.000 claims description 2
- QXJSBBXBKPUZAA-UHFFFAOYSA-N isooleic acid Natural products CCCCCCCC=CCCCCCCCCC(O)=O QXJSBBXBKPUZAA-UHFFFAOYSA-N 0.000 claims description 2
- 229940041616 menthol Drugs 0.000 claims description 2
- 229920000609 methyl cellulose Polymers 0.000 claims description 2
- 239000001923 methylcellulose Substances 0.000 claims description 2
- FUZZWVXGSFPDMH-UHFFFAOYSA-N n-hexanoic acid Natural products CCCCCC(O)=O FUZZWVXGSFPDMH-UHFFFAOYSA-N 0.000 claims description 2
- 229920005615 natural polymer Polymers 0.000 claims description 2
- 239000002736 nonionic surfactant Substances 0.000 claims description 2
- ZQPPMHVWECSIRJ-KTKRTIGZSA-N oleic acid Chemical compound CCCCCCCC\C=C/CCCCCCCC(O)=O ZQPPMHVWECSIRJ-KTKRTIGZSA-N 0.000 claims description 2
- WVDDGKGOMKODPV-ZQBYOMGUSA-N phenyl(114C)methanol Chemical compound O[14CH2]C1=CC=CC=C1 WVDDGKGOMKODPV-ZQBYOMGUSA-N 0.000 claims description 2
- 235000019422 polyvinyl alcohol Nutrition 0.000 claims description 2
- 239000001267 polyvinylpyrrolidone Substances 0.000 claims description 2
- 229920000036 polyvinylpyrrolidone Polymers 0.000 claims description 2
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 claims description 2
- 230000001105 regulatory effect Effects 0.000 claims description 2
- 229910052708 sodium Inorganic materials 0.000 claims description 2
- 239000011734 sodium Substances 0.000 claims description 2
- 239000001509 sodium citrate Substances 0.000 claims description 2
- NLJMYIDDQXHKNR-UHFFFAOYSA-K sodium citrate Chemical compound O.O.[Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O NLJMYIDDQXHKNR-UHFFFAOYSA-K 0.000 claims description 2
- 238000006467 substitution reaction Methods 0.000 claims description 2
- 229920001059 synthetic polymer Polymers 0.000 claims description 2
- 150000003505 terpenes Chemical class 0.000 claims description 2
- RTKIYNMVFMVABJ-UHFFFAOYSA-L thimerosal Chemical compound [Na+].CC[Hg]SC1=CC=CC=C1C([O-])=O RTKIYNMVFMVABJ-UHFFFAOYSA-L 0.000 claims description 2
- 229940033663 thimerosal Drugs 0.000 claims description 2
- 239000000230 xanthan gum Substances 0.000 claims description 2
- 235000010493 xanthan gum Nutrition 0.000 claims description 2
- 229920001285 xanthan gum Polymers 0.000 claims description 2
- 229940082509 xanthan gum Drugs 0.000 claims description 2
- 239000000758 substrate Substances 0.000 claims 2
- 229960002233 benzalkonium bromide Drugs 0.000 claims 1
- 229960000686 benzalkonium chloride Drugs 0.000 claims 1
- KHSLHYAUZSPBIU-UHFFFAOYSA-M benzododecinium bromide Chemical compound [Br-].CCCCCCCCCCCC[N+](C)(C)CC1=CC=CC=C1 KHSLHYAUZSPBIU-UHFFFAOYSA-M 0.000 claims 1
- CADWTSSKOVRVJC-UHFFFAOYSA-N benzyl(dimethyl)azanium;chloride Chemical compound [Cl-].C[NH+](C)CC1=CC=CC=C1 CADWTSSKOVRVJC-UHFFFAOYSA-N 0.000 claims 1
- 238000005303 weighing Methods 0.000 claims 1
- 230000000694 effects Effects 0.000 abstract description 4
- 230000000638 stimulation Effects 0.000 abstract description 2
- 230000017531 blood circulation Effects 0.000 abstract 1
- 231100001231 less toxic Toxicity 0.000 abstract 1
- 239000002502 liposome Substances 0.000 abstract 1
- 210000004400 mucous membrane Anatomy 0.000 abstract 1
- 239000002245 particle Substances 0.000 abstract 1
- 239000003755 preservative agent Substances 0.000 abstract 1
- 230000002335 preservative effect Effects 0.000 abstract 1
- 238000012856 packing Methods 0.000 description 6
- 238000005070 sampling Methods 0.000 description 6
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- 238000010521 absorption reaction Methods 0.000 description 3
- 230000002496 gastric effect Effects 0.000 description 3
- 230000035935 pregnancy Effects 0.000 description 3
- 238000010579 first pass effect Methods 0.000 description 2
- 210000001035 gastrointestinal tract Anatomy 0.000 description 2
- 210000004185 liver Anatomy 0.000 description 2
- 206010000084 Abdominal pain lower Diseases 0.000 description 1
- 208000037853 Abnormal uterine bleeding Diseases 0.000 description 1
- 206010006187 Breast cancer Diseases 0.000 description 1
- 208000026310 Breast neoplasm Diseases 0.000 description 1
- 206010008342 Cervix carcinoma Diseases 0.000 description 1
- 206010014759 Endometrial neoplasm Diseases 0.000 description 1
- 201000009273 Endometriosis Diseases 0.000 description 1
- 206010033128 Ovarian cancer Diseases 0.000 description 1
- 206010061535 Ovarian neoplasm Diseases 0.000 description 1
- 208000006105 Uterine Cervical Neoplasms Diseases 0.000 description 1
- 206010046798 Uterine leiomyoma Diseases 0.000 description 1
- 206010047700 Vomiting Diseases 0.000 description 1
- 208000022531 anorexia Diseases 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 201000008275 breast carcinoma Diseases 0.000 description 1
- 210000001736 capillary Anatomy 0.000 description 1
- 230000015556 catabolic process Effects 0.000 description 1
- 201000010881 cervical cancer Diseases 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 206010061428 decreased appetite Diseases 0.000 description 1
- 238000006731 degradation reaction Methods 0.000 description 1
- 208000002173 dizziness Diseases 0.000 description 1
- 238000012377 drug delivery Methods 0.000 description 1
- 201000003914 endometrial carcinoma Diseases 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 230000010224 hepatic metabolism Effects 0.000 description 1
- 210000001365 lymphatic vessel Anatomy 0.000 description 1
- 210000004877 mucosa Anatomy 0.000 description 1
- 238000007086 side reaction Methods 0.000 description 1
- 239000000934 spermatocidal agent Substances 0.000 description 1
- 230000008337 systemic blood flow Effects 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 230000008673 vomiting Effects 0.000 description 1
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- Medicinal Preparation (AREA)
Abstract
The vagina administrated mifepristone preparation for birth control and health reproduction consists of mifepristone or nanometer mifepristone liposome particle as main component, excipient, osmosis promoter, pH regulator, preservative, surfactant, solvent, water and other pharmaceutically acceptable components, and may be prepared into gel, film or other preparation forms. The vagina administrated mifepristone preparation is absorbed through vagina mucous membrane into blood circulation, and has high bioavailability, lowered dosage, less toxic side effect and less stimulation.
Description
Affiliated field:
The invention belongs to medical technical field, relate to a kind of vagina administration mifepristone preparation and composition and preparation method that is used for family planning and healthy reproduction aspect.
Background technology:
Mifepristone (Mifepristone) be by French Roussel-Uclaf company in nineteen eighty-two succeed in developing (former code Ru-486) a kind ofly have gestation and an active oral medicine of Antiglucocorticoid through gastrointestinal absorption.Mifepristone uses at clinical expansion as the termination of early pregnancy medicine at first, and its effectiveness and safety are confirmed.Along with intensification to its understanding, mifepristone now has been widely used in family planning and the healthy reproduction at present, for example: stop in the treatment of (early, middle and late phase) gestation, emergency contraception and some gynaecopathias, as: aspects such as hysteromyoma, abnormal uterine bleeding, endometriosis, carcinoma of endometrium, cervical cancer, ovarian cancer, breast carcinoma, and obtained certain effect, become important drugs treatment means gradually in each clinical speciality extensive use of gynecological.According to another report, mifepristone also has certain spermicide effect.Yet this medicine now is oral formulations, and mifepristone is through gastrointestinal absorption, liver metabolism, first-pass effect takes place, its bioavailability only is 30-40%, and different degree exist gastrointestinal reaction, as: feel sick, senses of discomfort such as anorexia, vomiting and dizziness, weak and lower abdominal pain.And the vagina administration preparation can directly be placed on intravaginal and enter part or systemic blood circulation by the vaginal mucosa absorption during use.Vagina has abundant blood capillary and lymphatic vessel, and vagina do not have tangible teleneuron, and that the misery during administration stimulates is little, drug utilization degree height, toxic and side effects are little, is effective medicament slow release position.Yet the mifepristone medicine is absence of vagina drug-delivery preparation always at present, is therefore using vagina administration mifepristone preparation provided by the invention will have vast market prospect aspect family planning and the healthy reproduction.The invention of this vagina administration mifepristone preparation also provides new dosage form for the application of mifepristone medicine in family planning and healthy reproduction, and new route of administration also is provided simultaneously.
Summary of the invention:
The purpose of this invention is to provide a kind of vagina administration mifepristone preparation and composition and preparation method.
The present invention is grouped into by pharmaceutically acceptable one-tenth such as host, excipient (drug matrices or carrier), penetration enhancer, pH regulator agent, antiseptic, surfactant, solvent, water.According to the difference of preparation method, can be made into: the dosage form of gel, membrane etc.
Vagina administration mifepristone preparation of the present invention composed as follows, composition and content to its composition in scope of the present invention are adjusted also in the present invention.
Form content (weight %)
Host 0.005-60
Excipient (drug matrices or carrier) 0.1-95
Antiseptic 0-5
Penetration enhancer 0.1-10
It is the amount of 3-6 that pH value is regulated in the pH regulator agent
Surfactant 0-20
Solvent 1-70
Water surplus
Host described in the present invention comprises: mifepristone, mifepristone solid lipid nanoparticle etc.;
Excipient described in the present invention is the excipient (drug matrices or carrier) of dosage forms such as medicinal gel, membrane, and it comprises: one of synthetic or natural polymer such as carbopol (carbomer), starch based derivant (carboxymethyl starch sodium, hetastarch, pregelatinized Starch), carboxymethyl cellulose, cellulose derivative (methylcellulose, hydroxypropyl emthylcellulose, hydroxypropyl cellulose or LS-HPC are hydroxypropyl cellulose, the hydroxyethyl-cellulose of low degree of substitution), polyvinyl alcohol, polyvinylpyrrolidone, alginic acid, xanthan gum or mix;
Penetration enhancer described in the present invention comprises: azone class such as laurocapram, terpenoid such as menthol, Borneolum Syntheticum etc.;
PH regulator agent described in the present invention comprises: sodium hydroxide, potassium hydroxide, aluminium hydroxide, triethanolamine and/or hydrochloric acid, citric acid, sodium citrate, glacial acetic acid etc.;
Antiseptic described in the present invention be selected from following:the mixture of one or more in benzyl alcohol, chlorobutanol, thimerosal, hibitane, benzene Zha Lv , Ben Zha Xiu , Metagin (second, the third) ester etc.;
Solvent described in the present invention is one or more the mixture that adopts in dichloromethane, methanol, ethanol, ethyl acetate, propylene glycol, the glycerol etc.;
The nonionic surfactant that surfactant described in the present invention is, as: one or more in polyoxyethylene castor oil double glyceride, Arlacel-20, polyoxyethylene mono laurate Pyrusussuriensis ester, polyoxyethylene list oleic acid Pyrusussuriensis ester, Brij30, polyoxyethylene (10) monolaurate, polyoxyethylene castor oil, certain herbaceous plants with big flowers acid glyceryl laurate ester or the caproic acid glyceryl laurate ester.
The preparation method and the step of vagina administration mifepristone preparation of the present invention are as follows:
1, load weighted host is dissolved in makes host solution in the solvent, or host, surfactant be dissolved in make host solution in the solvent;
2, load weighted excipient (drug matrices or carrier) is added water and make it abundant swelling, the host solution that adds required adjuvant such as antiseptic, penetration enhancer and above-mentioned 1 step, make it uniform mixing, making its pH value with the adjusting of PH regulator is 3-6, adds water to total amount, stir, deaeration, make gel preparation, carry out Quality Identification, making every ml gel contain mifepristone is 1-300mg, behind the accreditation, promptly get the vagina administration mifepristone gel preparation;
3, load weighted excipient (drug matrices or carrier) is added water and make it abundant swelling, the host solution that adds required adjuvant such as antiseptic, penetration enhancer and above-mentioned 1 step, add water to total amount, stirring makes it mix homogeneously, deaeration, film, drying, demoulding, section, make film preparation, carry out Quality Identification, making every film contain mifepristone is 1-300mg, behind the accreditation, promptly gets the vagina administration mifepristone film preparation;
Vagina administration mifepristone preparation of the present invention has following advantage: (1) is strong with the medicinal part affinity, adhesiveness good, the holdup time is long; (2) can be widely used in family planning and the healthy reproduction; (3) can avoid the first pass effect of liver effectively, improve its bioavailability; (4) can avoid stimulation and the side reaction of medicine effectively to human gastrointestinal tract; (5) can avoid the Degradation of gastrointestinal tract effectively to medicine; (6) infringement that can avoid medicine that liver is brought effectively; (7) application for the mifepristone medicine provides new dosage form and route of administration.
The specific embodiment:
The following examples will the present invention is further elaborated, but do not limit content of the present invention.
Embodiment 1:
Get ethanol 30g, add mifepristone 25g, stir and make dissolving.Get carbopol (carbomer) 10g and add entry 800g and stir and to make abundant swelling, add laurocapram 20g, methyl hydroxybenzoate 1.8g, and above-mentioned dissolved mifepristone solution, uniform mixing, regulate with triethanolamine that to make its pH value be 4, add entry, stir, deaeration to 1000g.Quality Identification is carried out in sampling, and qualified back packing promptly gets the vagina administration mifepristone gel preparation.
Embodiment 2:
Get ethanol 50g, add mifepristone 50g, stir and make dissolving.Getting hydroxypropyl emthylcellulose 15g, carbopol (carbomer) 5g adds entry 800g and stirs and to make swelling, add laurocapram 30g, methyl hydroxybenzoate 1.8g, and above-mentioned dissolved mifepristone solution, uniform mixing, making its pH value with the triethanolamine adjusting is 4, add entry to 1000g, stir, deaeration.Quality Identification is carried out in sampling, and qualified back packing promptly gets the vagina administration mifepristone gel preparation.
Embodiment 3:
Get ethanol 30g, add mifepristone solid lipid nanoparticle 20g, stir and make dissolving.Getting carbopol (carbomer) 5g, alginic acid 10g adds entry 800g and stirs and to make swelling, add laurocapram 15g, methyl hydroxybenzoate 1.5g, and above-mentioned dissolved mifepristone solid lipid nanoparticle solution, uniform mixing, making its pH value with the triethanolamine adjusting is 4, add entry to 1000g, stir, deaeration.Quality Identification is carried out in sampling, and qualified back packing promptly gets the vagina administration mifepristone gel preparation.
Embodiment 4
Get ethanol 20g, add mifepristone 15g, Arlacel-20 7g stirring and make dissolving.Getting hydroxypropyl emthylcellulose 20g, carbopol (carbomer) 5g adds entry 300g and stirs and to make swelling, add laurocapram 3g, glycerol 50g, and above-mentioned dissolved mifepristone solution, add entry to 500g, stir, deaeration, film, drying, demoulding, section, Quality Identification is carried out in sampling, qualified back packing promptly gets the vagina administration mifepristone film preparation.
Embodiment 5:
Get ethanol 25g, add mifepristone 20g, stir and make dissolving.Getting polyvinyl alcohol 40g, carbopol (carbomer) 10g adds entry 320g and stirs and to make swelling, add laurocapram 3g, glycerol 25g, and above-mentioned dissolved mifepristone solution, add entry to total amount 500g, stir, deaeration, film, drying, demoulding, section, Quality Identification is carried out in sampling, qualified back packing promptly gets the vagina administration mifepristone film preparation.
Embodiment 6:
Get ethanol 20g, add mifepristone solid lipid nanoparticle 10g, stir and make dissolving.Getting polyvinyl alcohol 30g, alginic acid 20g adds entry 300g and stirs and to make swelling, add laurocapram 2g, glycerol 25g, and above-mentioned dissolved mifepristone solid lipid nanoparticle solution, add entry to total amount 500g, stir, deaeration, film, drying, demoulding, section, Quality Identification is carried out in sampling, and qualified back packing promptly gets the vagina administration mifepristone film preparation.
Claims (3)
1, vagina administration mifepristone preparation and composition thereof and preparation method is characterized in that consist of (content, the weight %) of this vagina administration mifepristone preparation:
Form content (weight %)
Host 0.005-60
Excipient (drug matrices or carrier) 0.1-95
Antiseptic 0-5
Penetration enhancer 0.1-10
It is the amount of 3-6 that pH value is regulated in the pH regulator agent
Surfactant 0-20
Solvent 1-70
Water surplus
2, vagina administration mifepristone preparation according to claim 1 and composition and preparation method is characterized in that described host comprises: mifepristone, mifepristone solid lipid nanoparticle etc.; Described excipient is the excipient (drug matrices or carrier) of dosage forms such as medicinal gel, membrane, and it comprises: one of synthetic or natural polymer such as carbopol (carbomer), starch based derivant (carboxymethyl starch sodium, hetastarch, pregelatinized Starch), carboxymethyl cellulose, cellulose derivative (methylcellulose, hydroxypropyl emthylcellulose, hydroxypropyl cellulose or LS-HPC are hydroxypropyl cellulose, the hydroxyethyl-cellulose of low degree of substitution), polyvinyl alcohol, polyvinylpyrrolidone, alginic acid, xanthan gum or mix; Described penetration enhancer comprises: azone class such as laurocapram, terpenoid such as menthol, Borneolum Syntheticum etc.; Described pH regulator agent comprises: sodium hydroxide, potassium hydroxide, aluminium hydroxide, triethanolamine and/or hydrochloric acid, citric acid, sodium citrate, glacial acetic acid etc.; Described antiseptic be selected from following: the mixture of one or more in benzyl alcohol, chlorobutanol, thimerosal, hibitane, benzalkonium chloride, benzalkonium bromide, Metagin (second, the third) ester etc.; Described solvent is one or more the mixture that adopts in dichloromethane, methanol, ethanol, ethyl acetate, propylene glycol, the glycerol etc.; The nonionic surfactant that described surfactant is, as: one or more in polyoxyethylene castor oil double glyceride, Arlacel-20, polyoxyethylene mono laurate Pyrusussuriensis ester, polyoxyethylene list oleic acid Pyrusussuriensis ester, Brij30, polyoxyethylene (10) monolaurate, polyoxyethylene castor oil, certain herbaceous plants with big flowers acid glyceryl laurate ester or the caproic acid glyceryl laurate ester.
3, vagina administration mifepristone preparation according to claim 1 and composition and preparation method is characterized in that this vagina administration mifepristone preparation can be prepared into the dosage form of gel, membrane etc., and its preparation method is as follows:
(1), form weighing, host is dissolved in makes host solution in the solvent, or host, surfactant be dissolved in make host solution in the solvent by vagina administration mifepristone preparation of the present invention;
(2), load weighted substrate is added water and make it abundant swelling, add the host solution of required adjuvant such as antiseptic, penetration enhancer and above-mentioned (1) step, make it uniform mixing, making its pH value with the adjusting of PH regulator is 3-6, add water to total amount, stir, gel preparation is made in deaeration, carry out Quality Identification, making every ml gel contain mifepristone is 0.1-300mg, behind the accreditation, promptly gets the vagina administration mifepristone gel preparation;
(3), load weighted substrate is added water and make it abundant swelling, the host solution that adds required adjuvant such as antiseptic, penetration enhancer and above-mentioned (1) step, add water to total amount, stirring makes it mix homogeneously, deaeration, film, drying, demoulding, section, make film preparation, carry out Quality Identification, making every film contain mifepristone is 0.1-300mg, behind the accreditation, promptly gets the vagina administration mifepristone film preparation.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 200610042252 CN1846703A (en) | 2006-02-13 | 2006-02-13 | Vagina administration mifepristone prepn and its composition and prepn process |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 200610042252 CN1846703A (en) | 2006-02-13 | 2006-02-13 | Vagina administration mifepristone prepn and its composition and prepn process |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN1846703A true CN1846703A (en) | 2006-10-18 |
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN 200610042252 Pending CN1846703A (en) | 2006-02-13 | 2006-02-13 | Vagina administration mifepristone prepn and its composition and prepn process |
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| WO2009037704A1 (en) * | 2007-09-20 | 2009-03-26 | Bio-Pro Medical Ltd. | Compositions and means for treating uterine leiomyomata, leiomyoma, myoma, uterine fibroids, endrometriosis, adenomyosis and related disorders by mifepristone |
| CN102048681A (en) * | 2010-12-20 | 2011-05-11 | 广州共禾医药科技有限公司 | Mifepristone slow release preparation characterized by gastric stasis and preparation method thereof |
| CN101181227B (en) * | 2007-12-10 | 2012-05-30 | 沈阳药科大学 | Solid lipid nanometer particle in-situ gel rubber preparations of biological adherent cyclosporine A and preparation method thereof |
| US20130018027A1 (en) * | 2010-03-22 | 2013-01-17 | Repros Therapeutics Inc. | Compositions and methods for non-toxic delivery of antiprogestins |
| CN102974025A (en) * | 2012-12-11 | 2013-03-20 | 天津市聚星康华医药科技有限公司 | Disposable cervical dilator attached with medicine film |
| CN103127515A (en) * | 2011-11-22 | 2013-06-05 | 湖南九典制药有限公司 | Traditional Chinese medicine cataplasm matrix composition and preparation method thereof |
| CN105796572A (en) * | 2014-08-25 | 2016-07-27 | 郭曙平 | Contraceptive and preparation method thereof |
| US9545411B2 (en) | 2012-11-02 | 2017-01-17 | Repros Therapeutics Inc. | Methods and compositions for treating progesterone-dependent conditions |
| US10328022B2 (en) | 2012-05-31 | 2019-06-25 | Repros Therapeutics Inc. | Formulations and methods for vaginal delivery of antiprogestins |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| JP2010540430A (en) * | 2007-09-20 | 2010-12-24 | バイオ−プロ メディカル リミテッド | Compositions and means for treating multiple uterine leiomyomas, leiomyomas, fibroids, uterine fibroids, endometriosis, adenomyosis and associated disorders with mifepristone |
| US20110208118A1 (en) * | 2007-09-20 | 2011-08-25 | Bio-Pro Medical Ltd. | Compositions and means for treating uterine leiomyomata, leiomyoma, myoma, uterine fibroids, endometriosis, adenomyosis and related disorders by mifepristone |
| WO2009037704A1 (en) * | 2007-09-20 | 2009-03-26 | Bio-Pro Medical Ltd. | Compositions and means for treating uterine leiomyomata, leiomyoma, myoma, uterine fibroids, endrometriosis, adenomyosis and related disorders by mifepristone |
| AU2008300199B2 (en) * | 2007-09-20 | 2013-09-12 | Lapidot Medical Import And Marketing Ltd | Compositions and means for treating uterine leiomyomata, leiomyoma, myoma, uterine fibroids, endrometriosis, adenomyosis and related disorders by mifepristone |
| CN101181227B (en) * | 2007-12-10 | 2012-05-30 | 沈阳药科大学 | Solid lipid nanometer particle in-situ gel rubber preparations of biological adherent cyclosporine A and preparation method thereof |
| US20130018027A1 (en) * | 2010-03-22 | 2013-01-17 | Repros Therapeutics Inc. | Compositions and methods for non-toxic delivery of antiprogestins |
| CN102048681A (en) * | 2010-12-20 | 2011-05-11 | 广州共禾医药科技有限公司 | Mifepristone slow release preparation characterized by gastric stasis and preparation method thereof |
| CN103127515A (en) * | 2011-11-22 | 2013-06-05 | 湖南九典制药有限公司 | Traditional Chinese medicine cataplasm matrix composition and preparation method thereof |
| US10328022B2 (en) | 2012-05-31 | 2019-06-25 | Repros Therapeutics Inc. | Formulations and methods for vaginal delivery of antiprogestins |
| US9545411B2 (en) | 2012-11-02 | 2017-01-17 | Repros Therapeutics Inc. | Methods and compositions for treating progesterone-dependent conditions |
| CN102974025A (en) * | 2012-12-11 | 2013-03-20 | 天津市聚星康华医药科技有限公司 | Disposable cervical dilator attached with medicine film |
| CN102974025B (en) * | 2012-12-11 | 2015-09-30 | 天津市聚星康华医药科技有限公司 | A kind of one-off cervix dilator with medicine film |
| CN105796572A (en) * | 2014-08-25 | 2016-07-27 | 郭曙平 | Contraceptive and preparation method thereof |
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